Process for depigmenting keratin materials using thiopyridinone compounds

ABSTRACT

The invention relates to a cosmetic process for depigmenting, lightening and/or whitening keratin materials, in particular the skin, which comprises the application of a cosmetic composition comprising a compound of formula (I): or its tautomer form of formula (I) in which: R 1  and R 2 , which may be identical or different, denote a radical chosen from: a) a hydrogen atom; b) a C 1 -C 20  alkyl group optionally interrupted with N, S or O, optionally substituted with one or more group(s) chosen from —OR 3 , —SR 3 , —NR 3 R 4 , —CONHR3; —COOR 3 ; and an aryl group optionally substituted with one or more hydroxyls and/or with one or more C 1 -C 8  alkoxy radicals; c) a C 1 -C 8  alkyl group substituted with a C 5 -C 12  aryl radical optionally substituted with one or more hydroxyls and/or with one or more C 1 -C 8  alkoxy radicals; d) a phenyl group optionally substituted with one or more hydroxyls and/or with one or N more C1-C8 alkoxy radicals; R3 denoting H or a C 1 -C 5  alkyl group, R 4  denoting H, a C 1 -C 5  hydrocarbon-based group or an acetyl group; it being possible for R 1  and R 2  to form, with the nitrogen atom which bears them, a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine. The invention also relates to the cosmetic use of a compound (I) or (I) as a whitening, lightening and/or depigmenting agent for keratin materials.

The present invention relates to a cosmetic treatment process inparticular for depigmenting and/or whitening the skin, that employs atleast one compound of thiopyridinone type.

At various periods in their life, certain people develop darker and/ormore coloured marks on their skin, and more especially on the hands,which gives the skin a heterogeneous appearance. These marks are due inparticular to a high concentration of melanin in the keratinocyteslocated at the surface of the skin.

The use of harmless topical depigmenting substances which exhibit goodefficacy is especially desirable with a view to treating pigmentarymarks.

The mechanism of formation of skin pigmentation, i.e. of the formationof melanin, is particularly complex and involves, schematically, thefollowing principal steps:

Tyrosine--->Dopa--->Dopaquinone--->Dopachrome--->Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductaseEC 1.14.18.1) is the essential enzyme involved in this series ofreactions. It catalyzes in particular the reaction converting tyrosineto Dopa (dihydroxyphenylalanine) by virtue of its hydroxylase activity,and the reaction converting Dopa to dopaquinone by virtue of its oxidaseactivity. This tyrosinase acts only when it is in the mature form, underthe action of certain biological factors.

A substance is acknowledged to be depigmenting if it acts directly onthe vitality of epidermal melanocytes, where melanogenesis takes place,and/or if it interferes with one of the steps of melanin biosynthesis,either by inhibiting one of the enzymes involved in melanogenesis, or bybeing inserted as a structural analogue of one of the chemical compoundsof the melanin synthesis chain, which chain may then be blocked and thusensure depigmentation.

Arbutin, niacinamide and kojic acid are known as skin depigmentingagents.

Substances have been sought which exhibit an effective depigmentingaction, in particular greater than that of arbutin, niacinamide andkojic acid.

In this regard, the applicant has found, surprisingly and unexpectedly,that certain thiopyridinone compounds exhibit good depigmentingactivity, even at low concentration.

The subject of the invention is therefore a nontherapeutic cosmeticprocess for depigmenting, lightening and/or whitening keratin materials,in particular the skin, which comprises the application of a cosmeticcomposition comprising, in a physiologically acceptable medium, at leastone compound of formula (I) as defined hereinafter.

The invention also relates to the nontherapeutic cosmetic use of acompound of formula (I) as a whitening, lightening and/or depigmentingagent for keratin materials, in particular the skin.

The compounds used according to the invention allow effectivedepigmenting and/or lightening, or even whitening, of the skin of humanbeings. They are in particular intended to be applied to the skin ofindividuals exhibiting brownish pigmentation marks or senescence marks,or to the skin of individuals who wish to combat the appearance of abrownish colour arising from melanogenesis.

They may also allow depigmentation and/or lightening of body hair, theeyelashes, head hair and also the lips and/or the nails.

The compounds used according to the invention therefore correspond toformula (I) or (I′) below:

in which:R₁ and R₂, which may be identical or different, denote a radical chosenfrom:

-   -   a) a hydrogen atom;    -   b) a saturated linear C₁-C₂₀ or branched C₃-C₂₀ or unsaturated        C₂-C₂₀ alkyl group, optionally interrupted with one or more        heteroatoms chosen from N, S and O, and/or optionally        substituted with one or more groups, which may be identical or        different, chosen from:        -   i) —OR₃        -   ii) —SR₃,        -   iii) —NR₃R₄        -   iv) —CONHR₃        -   v) —COOR₃;        -   vi) a C₅-C₁₂ aryl group optionally substituted with one or            more hydroxyls and/or with one or more C₁-C₈ alkoxy            radicals;    -   c) a saturated C₁-C₈ alkyl group substituted with a C₅-C₁₂ aryl        radical optionally substituted with one or more hydroxyls and/or        with one or more C₁-C₈ alkoxy radicals;    -   d) a phenyl group optionally substituted with one or more        hydroxyls and/or with one or more C₁-C₈ alkoxy radicals;        R₃ denoting a hydrogen atom or a saturated linear C₁-C₅ or        branched C₃-C₅ or unsaturated C₂-C₅ hydrocarbon-based group,        R₄ denoting a hydrogen atom; a saturated linear C₁-C₅ or        branched C₃-C₅ hydrocarbon-based group; or an acetyl group;        it being possible for R₁ and R₂ to form, with the nitrogen atom        which bears them, a ring chosen from pyrrolidine, pyrroline,        piperidine, piperazine, morpholine, thiomorpholine and azepine;        and also the salts thereof, the solvates thereof and the optical        isomers thereof, and the racemates thereof.

The compound (I′) is the tautomer form of the compound (I) when atautomeric equilibrium exists according to the following scheme:

The salts of the compounds of formula (I) or (I′) comprise theconventional nontoxic salts of said compounds, such as those formed fromacid or from base.

As salts of the compound of formula (I) or (I′), when it comprises aquaternizable nitrogen atom), mention may be made of:

a) the salts obtained by addition of the compound (I) or (I′) with aninorganic acid, in particular chosen from hydrochloric acid, boric acid,hydrobromic acid, hydrioic acid, sulphuric acid, nitric acid, carbonicacid, phosphoric acid and tetrafluoroboric acid;b) or the salts obtained by addition of the compound (I) or (I′) with anorganic acid, in particular chosen from acetic acid, propionic acid,succinic acid, fumaric acid, lactic acid, glycolic acid, citric acid,gluconic acid, salicylic acid, tartaric acid, terephthalic acid,methylsulphonic acid, ethylsulphonic acid, benzene-sulphonic acid,toluenesulphonic acid and triflic acid.

Mention may also be made of the salts obtained by addition of thecompound of formula (I) or (I′) (when it comprises an acid group) withan inorganic base, such as sodium hydroxide, potassium hydroxide,calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithiumhydroxide, and sodium, potassium or calcium carbonates or hydrogencarbonates, for example;

or with an organic base, such as a primary, secondary or tertiaryalkylamine, for example triethylamine or butylamine. This primary,secondary or tertiary alkylamine may comprise one or more nitrogenand/or oxygen atoms and may therefore comprise, for example, one or morealcohol functions; mention may in particular be made of2-amino-2-methylpropanol, ethanolamine, triethanolamine,2-dimethylaminopropanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol and3-(dimethylamino)propylamine.

Mention may also be made of amino acids such as, for example, lysine,arginine, guanidine, glutamic acid or aspartic acid.

Advantageously, the salts of the compounds of formula (I) or (I′) (whenit comprises an acid group) may be chosen from alkali metal salts oralkaline earth metal salts, such as sodium, potassium, calcium ormagnesium salts; and ammonium salts.

Advantageously, the salts of the compounds of formula (I) or (I′) (whenit comprises a quaternizable nitrogen atom) can be chosen from halidessuch as chloride or bromide; and citrates, acetates, succinates,phosphates, lactates and tartrates.

The acceptable solvates of the compounds described in the presentinvention comprise conventional solvates such as those formed during thepreparation of said compounds as a result of the presence of solvents.By way of example, mention may be made of the solvates resulting fromthe presence of water or of linear or branched alcohols such as ethanolor isopropanol.

The optical isomers are in particular enantiomers and diastereoisomers.

Preferentially, the linear or branched groups can be chosen from:methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl,hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl andeicosyl.

More preferentially, the saturated linear or branched alkyl groups canbe chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl,tert-butyl, pentyl, hexyl, heptyl and octyl.

Preferentially, the C₁-C₄ alkoxy groups can be chosen from methoxy,ethoxy, propoxy and butoxy, and even more preferentially methoxy.

The compounds of formula (I) can be obtained, in a known manner, byreacting 2-mercaptonicotinic acid and an amine of formula HNR₁R₂ (R₁ andR₂ having the meanings described above), in particular in the presenceof a base such as carbonyldiimidazole.

The compounds of formula (I) can also be obtained, in a known manner, byreacting 2-mercaptonicotinic acid or 2-chloronicotinic acid with anamine of formula HNR₁R₂ (R₁ and R₂ having the meanings described above),in particular in the presence of an agent for activating carboxylicacids according to the conventional methods for activating acids(described, for example, in Comprehensive Organic Transformation by R.Larock, published by Wiley VCH, in the chapter Interconversion ofnitriles, carboxylic acids and derivatives). Use is preferably made ofan agent for activating carboxylic acids which makes it possible to forman acid chloride (for example, using thionyl chloride or oxalylchloride, or 1-chloro-N,N,2-trimethyl-1-propenamine) or to form a mixedanhydride (using alkyl chloroformates), or carbodiimides or diethylcyanophosphate are used to form carbamimidates or acylphosphonates(Phosphorus in organic synthesis-XI, Amino acids and peptides-XXI,Reaction of diethyl phosphorocyanidate with carboxylic acids. A newsynthesis of carboxylic esters and amides, Tetrahedron, 32, 1976,2211-2217). When 2-chloronicotinic acid is used as starting reagent, thechloroamide obtained is then used in an exchange reaction betweenchlorine and sulphur by means of reagents such as NaSH, thiourea, sodiumthiosulphate or thioacetic acid (in basic medium).

Compounds of formula (I) or (I′) are described in the followingdocuments: EP-A-298752, WO03/014062, EP-A-298752, FR-A-2349591,EP-A-2555450, WO 03/014062 and WO 2008/012532, and in the publications

-   article A. Monge, V. Martinez-Merino; Synthesis of 2-substituted    3-Oxoisothiazolo[5,4-b]pyridines; J. heterocyclic. Chem, 22, 1353    (1985).-   article A. Dunn, R. Norrie; Synthesis of pyrido-1,3-thiazines;    Zeitschrift fur chemie 1988, vol 28, n^(o) 6, p 212/214.-   S. Andreae; J. Parkt. Chem. 339 (1997) 152-158;-   S. Gorsuch; Biorganic & Medicinal Chemistry 17 (2009) 467-474.-   A. Monge et al; J. Heterocyclic Che. 25, 23 (1988).-   M. Pregnolato; II Farmaco 55 (2000) 669-679.

Preferably, the compounds of the formula (I) or (I′) have the followingmeanings:

R₁ denotes a radical chosen from:

-   -   a) a hydrogen atom;    -   b) a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or unsaturated        C₂-C₁₀ alkyl group, optionally substituted with one or more OR₃        groups;        R₂ denotes a radical chosen from:    -   a) a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₃-C₇        alkyl group, optionally interrupted with one or more oxygen        atoms, preferably one, and/or optionally containing one or more        groups, which may be identical or different, chosen from:        -   i) —OR₃,        -   ii) —NR₃R₄,        -   iii) —CONHR₃,        -   iv) —COOR₃    -   b) a phenyl group optionally substituted with one or more        hydroxyls and/or with one or more C₁-C₃ alkoxy radicals;    -   c) a saturated C₁-C₅ alkyl group substituted with a phenyl        radical optionally substituted with one or more hydroxyls or        with one or more C₁-C₃ alkoxy radicals;        R₃ denoting a hydrogen atom or a saturated linear C₁-C₅ or        branched C₃-C₅ hydrocarbon-based group;        R₄ denoting a hydrogen atom or a saturated linear C₁-C₅ or        branched C₃-C₅ hydrocarbon-based group;        and the salts thereof, the solvates thereof and the optical        isomers thereof, and the racemates thereof.

Preferentially, the compounds of formula (I) or (I′) have the followingmeanings:

R₁ denotes a hydrogen atom or a linear C₁-C₄ alkyl radical optionallysubstituted with one or more hydroxyl groups;R₂ denotes a radical chosen from:

-   -   a) a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₇        alkyl group, optionally interrupted with an oxygen atom and/or        optionally containing a —CONH₂ group and/or optionally        substituted with one or more hydroxyl groups;    -   b) a phenyl group;    -   c) a saturated C₁-C₅ alkyl group substituted with a phenyl        radical optionally substituted with one or more hydroxyl or        C₁-C₃ alkoxy radicals;        and also the salts thereof, the solvates thereof and the optical        isomers thereof, and the racemates thereof.

More preferentially, the compounds of formula (I) or (I′) have thefollowing meanings:

R₁ denotes a hydrogen atom or a C₁-C₄ hydroxyalkyl group;R₂ denotes a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₆alkyl hydrocarbon-based group, optionally interrupted with an oxygenatom and/or optionally containing a —CONH₂ group and/or optionallysubstituted with a hydroxyl group; a phenyl group; or a saturated C₁-C₅alkyl group substituted with a phenyl radical itself optionallysubstituted with one or more hydroxyl or C₁-C₃ alkoxy radicals;and also the salts thereof, the solvates thereof and the optical isomersthereof, and the racemates thereof.

The subject of the invention is also the novel compounds of formulae(Ia) and (Ia′) corresponding to those of formula (I) or (I′) in which:

-   -   when R1 denotes a hydrogen atom, then R2 denotes a radical        chosen from unsaturated C₂-C₂₀ alkyls, cyclic C₇ alkyl radicals,        saturated linear C₁-C₂₀ or branched C₃-C₂₀ alkyls, substituted        with one or more identical or different —OR₃ groups, and        (C₁-C₂₀)alkylaryls substituted with one or more identical or        different —OR₃ groups, R₃ denoting a hydrogen atom or a        saturated linear C₁-C₅ or branched C₃-C₅ or unsaturated C₂-C₅        hydrocarbon-based group;    -   when R₁ denotes a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or        unsaturated C₂-C₁₀ alkyl group, optionally substituted with one        or more —OR₃ groups, then R₂ denotes a radical chosen from:        a) a saturated branched C₃-C₁₂ or cyclic C₃-C₇ alkyl group,        optionally interrupted with one or more oxygen atoms, preferably        one, and/or optionally containing one or more identical or        different —OR₃ groups,        R₃ denoting a hydrogen atom or an optionally hydroxylated,        saturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-based        group;        and also the salts thereof, the optical isomers thereof and the        racemates thereof.

Preferably, for the novel compounds of the formulae (Ia) and (Ia′):

-   -   when R1 denotes a hydrogen atom, then R2 denotes a radical        chosen from unsaturated C₂-C₂₀ alkyls, saturated linear C₁-C₂₀        or branched C₃-C₂₀ alkyls, substituted with one or more        identical or different —OR₃ groups, and (C₁-C₆)alkylphenyls        substituted with one or more identical or different —OR₃ groups,        R₃ denoting a hydrogen atom or a saturated linear C₁-C₅ or        branched C₃-C₅ or unsaturated C₂-C₅ hydrocarbon-based group;    -   when R1 denotes a saturated linear C₁-C₁₂ or branched C₃-C₁₀ or        unsaturated C₂-C₁₀ alkyl group, optionally substituted with one        or more —OR₃ groups, then R₂ denotes a radical chosen from:        a) a saturated branched C₃-C₁₂ or cyclic C₃-C₇ alkyl group,        optionally interrupted with one or more oxygen atoms, preferably        one, and/or optionally containing one or more identical or        different —OR₃ groups,        R₃ denoting a hydrogen atom or an optionally hydroxylated,        saturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-based        group,        and also the salts thereof, the optical isomers thereof and the        racemates thereof.

Preferably, for the novel compounds of formulae (Ia) and (Ia′):

-   -   when R₁ denotes a hydrogen atom, then R₂ denotes a radical        chosen from saturated linear C₁-C₂₀ or branched C₃-C₂₀ alkyls,        substituted with one or more identical or different —OR₃ groups,        and (C₁-C₆)alkylphenyls substituted with one or more identical        or different —OR₃ groups, R₃ denoting a hydrogen atom or a        saturated linear C₁-C₅ or branched C₃-C₅ or unsaturated C₂-C₅        hydrocarbon-based group;    -   when R₁ denotes a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or        unsaturated C₂-C₁₀ alkyl group, optionally substituted with one        or more —OR₃ groups, then R₂ denotes a radical chosen from:        a) a saturated branched C₃-C₁₂ or cyclic C₃-C₇ alkyl group,        optionally interrupted with one or more oxygen atoms, preferably        one, and/or optionally containing one or more identical or        different —OR₃ groups,        R₃ denoting a hydrogen atom or an optionally hydroxylated,        saturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-based        group.

Preferably, for the novel compounds of formulae (Ia) and (Ia′):

R₁ denotes a hydrogen atom and R₂ denotes a radical chosen from:a) a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₇ alkylgroup, substituted with one or more hydroxyl groups, and optionallyinterrupted with an oxygen atom, orR₁ denotes a linear C₁-C₄ alkyl radical optionally substituted with oneor more hydroxyl groups; and R₂ denotes a radical chosen from:a) a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₇ alkylgroup, substituted with one or more hydroxyl groups, and optionallyinterrupted with an oxygen atom.

Preferentially, for the novel compounds of formulae (Ia) and (Ia′):

R₁ denotes a hydrogen atom and R₂ denotes a saturated linear C₁-C₁₀ orbranched C₃-C₁₀ or cyclic C₅-C₆ alkyl hydrocarbon-based group,optionally interrupted with an oxygen atom and optionally substitutedwith a hydroxyl group, orR₁ denotes a C₁-C₄ hydroxyalkyl group;R₂ denotes a saturated linear C₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₆alkyl hydrocarbon-based group, optionally interrupted with an oxygenatom and optionally substituted with a hydroxyl group.

Among the compounds of formula (I), the following compounds arepreferably used:

No. Structure Chemical name CAS No.  1

N-methyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 91859- 74-4  2

N-ethyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 91859- 75-5  3

N-isopropyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide 91859- 76-6  4

N-propyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 330667- 56-6  5

N-(2-methylpropyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide1100027- 79-9  6

N-butyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 65282- 55-5  7

N-pentyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 330667- 57-7  8

N-octyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 91859- 77-7  9

N-nonyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 1031149- 44-6 10

N,N-dimethyl-2- mercaptonicotinamide 121650- 19-9 11

N-cyclopentyl-2- thioxo-1,2- dihydropyridine-3- carboxamide 1099928-42-3 12

N-cyclohexyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide 91859- 78-8 13

N-cycloheptyl-2- thioxo-1,2- dihydropyridine-3- carboxamide 451473- 73-714

N-phenyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 104857- 16-1 15

N-benzyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 91859- 79-9 16

N-[2-(4- methoxyphenyl)ethyl]- 2-thioxo-1,2- dihydropyridine-3-carboxamide 923682- 88-6 17

N-(3-ethoxypropyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide1061763- 97-02 18

N-(2-amino-2- oxoethyl)-2-thioxo-1,2- dihydropyridine-3- carboxamide497262- 18-7 19

N-(2-hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide 20

N,N-bis(2- hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide21

N-(2,3- dihydroxypropyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide22

N-(1,3- dihydroxypropan-2-yl)- 2-thioxo-1,2- dihydropyridine-3-carboxamide 23

N-ethyl-N-(2- hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3-carboxamide 24

N-(3-hydroxypropyl)- 2-thioxo-1,2- dihydropyridine-3- carboxamide 25

N-[2-(2- hydroxyethoxy)ethyl]- 2-thioxo-1,2- dihydropyridine-3-carboxamide 26

N-(3-methoxypropyl)- 2-thioxo-1,2- dihydropyridine-3- carboxamide 27

N,N-diethyl 2- mercaptonicotinamide 121050- 20-2 28

Ethyl N-[(2-thioxo-1,2- dihydropyridin-3- yl)carbonyl]alaninate 29

Ethyl N-[(2-thioxo-1,2- dihydropyridin-3- yl)carbonyl]phenyl alaninate30

N-[2- (dimethylamino)ethyl]- N-ethyl-2-thioxo-1,2- dihydropyridine-3-carboxamide

Among these compounds, the following compounds are more particularlypreferred:

No. Structure Chemical name  1

N-methyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide  2

N-ethyl-2-thioxo-1,2- dihydropyridine-3- carboxamide  3

N-isopropyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide  4

N-propyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide  5

N-(2-methylpropyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide  6

N-butyl-2-thioxo-1,2- dihydropyridine-3- carboxamide  7

N-pentyl-2-thioxo-1,2- dihydropyridine-3- carboxamide 11

N-cyclopentyl-2- thioxo-1,2- dihydropyridine-3- carboxamide 12

N-cyclohexyl-2- thioxo-1,2- dihydropyridine-3- carboxamide 13

N-cycloheptyl-2- thioxo-1,2- dihydropyridine-3- carboxamide 15

N-benzyl-2-thioxo- 1,2-dihydropyridine-3- carboxamide 16

N-[2-(4- methoxyphenyl)ethyl]- 2-thioxo-1,2- dihydropyridine-3-carboxamide 19

N-(2-hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide 20

N,N-bis(2- hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide21

N-(2,3- dihydroxypropyl)-2- thioxo-1,2- dihydropyridine-3- carboxamide23

N-ethyl-N-(2- hydroxyethyl)-2- thioxo-1,2- dihydropyridine-3-carboxamide 27

N,N-diethyl 2- mercaptonicotinamideand also the salts thereof, the optical isomers thereof and the solvatesthereof.

Compounds 1 and 10 are described in application EP-A-298752 as synthesisintermediates.

Compounds 2 to 8, 11 and 12 are described in FR-A-2555450.

Compound 14 is described in the article A. Monge, V. Martinez-Merino;Synthesis of 2-substituted 3-Oxoisothiazolo[5,4-b]pyridines; J.heterocyclic. Chem, 22, 1353 (1985).

Compounds 4, 6, 7 and 15 are described in the article A. Dunn, R.Norrie; Synthesis of pyrido-1,3-thiazines; Zeitschrift fur chemie 1988,vol 28, n° 6, p 212/214.

Compound 14 is described in the article A. Monge, V. Martinez-Merino;Synthesis of 2-substituted 3-Oxoisothiazolo[5,4-b]pyridines; J.heterocyclic. Chem, 22, 1353 (1985).

Compound 18 is described in WO-A-03/014062.

Compound 27 is described in EP 298752.

Compounds 2, 7, 12, 16, 21 and 27 are the most particularly preferred.

The compounds of formula (I) and/or (I′) according to the invention areof quite particular use in the cosmetics field.

The composition used according to the invention comprises a compound offormula (I) and/or (I′) as described above, in a physiologicallyacceptable medium.

The compound (I) and/or (I′) can be present in the composition usedaccording to the invention in an amount which can be between 0.01 and10% by weight, preferably between 0.1 and 5% by weight, in particularfrom 0.5 to 3% by weight, relative to the total weight of thecomposition.

The term “physiologically acceptable medium” is understood to mean amedium that is compatible with keratin materials of human beings, suchas the skin of the body or of the face, the lips, the mucous membranes,the eyelashes, the nails, the scalp and/or the hair.

The composition used according to the invention may thus comprise allthe adjuvants which are commonly employed in the cosmetics field.

Mention may in particular be made of water; organic solvents, inparticular C₂-C₆ alcohols; oils, in particular hydrocarbon-based oils,silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers;cosmetic active agents, UV screens, polymers, thickeners, preservatives,fragrances, bactericides, odour absorbers and antioxidants.

These optional cosmetic adjuvants may be present in the composition in aproportion of from 0.001 to 80% by weight, in particular 0.1 to 40% byweight, relative to the total weight of the composition. In any event,these adjuvants, and also the proportions thereof, will be chosen bythose skilled in the art in such a way that the advantageous propertiesof the compounds according to the invention are not, or notsubstantially, impaired by the envisaged addition.

As active agents, it will be advantageous to introduce into thecomposition used according to the invention at least one compound chosenfrom: desquamating agents; calmatives; organic or inorganicphotoprotective agents, moisturizers; depigmenting or propigmentingagents; anti-glycation agents; NO-synthase inhibitors; agents forstimulating the synthesis of dermal or epidermal macromolecules and/orpreventing degradation thereof; agents for stimulating fibroblast and/orkeratinocyte proliferation or stimulating keratinocyte differentiation;muscle relaxants and/or dermo-decontracting agents; tensioning agents;anti-pollution agents and/or free-radical scavengers; agents that act onthe microcirculation; agents that act on the energy metabolism of cells;and mixtures thereof.

Examples of such additional compounds are: retinol and derivativesthereof such as retinyl palmitate; ascorbic acid and derivatives thereofsuch as magnesium ascorbyl phosphate and ascorbyl glucoside; tocopheroland derivatives thereof such as tocopheryl acetate; nicotinic acid andprecursors thereof such as nicotinamide; ubiquinone; glutathione andprecursors thereof such as L-2-oxothiazolidine-4-carboxylic acid; plantextracts and in particular plant proteins and hydrolysates thereof, andalso plant hormones; marine extracts such as algal extracts; bacterialextracts; sapogenins such as diosgenin and wild yam extracts containingsame; ceramides; hydroxy acids such as salicylic acid and5-n-octanoylsalicylic acid; resveratrol; oligopeptides andpseudodipeptides and acyl derivatives thereof; manganese salts andmagnesium salts, in particular the gluconates; and mixtures thereof.

The term “desquamating agent” is intended to mean any compound capableof acting

-   -   either directly on desquamation by promoting exfoliation, such        as β-hydroxy acids, in particular salicylic acid and derivatives        thereof (including 5-n-octanoyl-salicylic acid); α-hydroxy        acids, such as glycolic acid, citric acid, lactic acid, tartaric        acid, malic acid or mandelic acid; urea; gentisic acid;        oligofucoses; cinnamic acid; Saphora japonica extract;        resveratrol;    -   or on the enzymes involved in the desquamation or degradation of        corneodesmosomes, glycosidases, stratum corneum chymotryptic        enzyme (SCCE) or even other proteases (trypsin,        chymotrypsin-like). Mention ay be made of agents for chelating        mineral salts: EDTA; N-acyl-N,N′,N′-ethylenediaminetriacetic        acid; am inosulphonic compounds and in particular (N-2        hydroxyethylpiperazine-N-2-ethane)sulphonic acid (HEPES);        derivatives of 2-oxothiazolidine-4-carboxylic acid        (procysteine); derivatives of alpha-amino acids of glycine type        (as described in EP-0 852 949, and also sodium methyl glycine        diacetate sold by BASF under the trade name Trilon M); honey;        sugar derivatives such as O-octanoyl-6-D-maltose and        N-acetylglucosamine.

The desquamating agents are generally present in the compositionaccording to the invention in proportions ranging from 0.01 to 15% byweight, preferably ranging from 0.1 to 10% by weight, relative to thetotal weight of the composition.

As calmatives that can be used in the composition according to theinvention, mention may be made of: pentacyclic triterpenes and extractsof plants (for example Glycyrrhiza glabra) containing them, for instanceβ-glycyrrhetinic acid and salts and/or derivatives thereof(glycyrrhetinic acid monoglucuronide, stearyl glycyrrhetinate,3-stearoyloxyglycyrrhetic acid), ursolic acid and salts thereof,oleanolic acid and salts thereof, betulinic acid and salts thereof, anextract of Paeonia suffruticosa and/or lactiflora, salicylic acid saltsand in particular zinc salicylate, phycosaccharides from the companyCodif, an extract of Laminaria saccharina, canola oil, bisabolol andcamomile extracts, allantoin, Sepivital EPC (phosphoric diester ofvitamin E and C) from SEPPIC, omega-3 unsaturated oils such as musk roseoil, blackcurrant oil, ecchium oil, fish oil, plankton extracts,capryloylglycine, Seppicalm VG (sodium palmitoylproline and Nympheaalba) from SEPPIC, an extract of Pygeum, an extract of Bosweffiaserrata, an extract of Centipeda cunnighami, an extract of Helianthusannuus, an extract of Linum usitatissimum, tocotrienols, extracts ofCola nitida, piperonal, an extract of clove, an extract of Epilobiumangustifolium, aloe vera, an extract of Bacopa moniera, phytosterols,cortisone, hydrocortisone, indomethacin and betamethasone.

The calmatives are generally present in the composition used accordingto the invention in proportions ranging from 0.01 to 15% by weight,preferably ranging from 0.1 to 10% by weight, relative to the totalweight of the composition.

The organic photoprotective agents are in particular chosen fromanthranilates; cinnamic derivatives; dibenzoylmethane derivatives;salicylic derivatives, camphor derivatives; triazine derivatives such asthose described in patent applications U.S. Pat. No. 4,367,390,EP863145, EP517104, EP570838, EP796851, EP775698, EP878469, EP933376,EP507691, EP507692, EP790243 and EP944624; benzophenone derivatives;β,β-diphenylacrylate derivatives; benzotriazole derivatives;benzalmalonate derivatives; benzimidazole derivatives; imidazolines;bis-benzoazolyl derivatives as described in patents EP669323 and U.S.Pat. No. 2,463,264; p-aminobenzoic acid (PABA) derivatives;methylenebis(hydroxyphenylbenzotriazole) derivatives as described inapplications U.S. Pat. No. 5,237,071, U.S. Pat. No. 5,166,355,GB2303549, DE19726184 and EP893119; screening polymers and screeningsilicones such as those described in particular in applicationWO-93/04665; and α-alkylstyrene-derived dimers such as those describedin patent application DE 19855649.

The inorganic photoprotective agents can in particular be chosen fromcoated or uncoated metal oxide pigments or nanopigments (average size ofthe primary particles generally between 5 nm and 100 nm, preferablybetween 10 nm and 50 nm), for instance nanopigments of titanium oxide(amorphous or crystallized in rutile and/or anatase form), of ironoxide, of zinc oxide, of zirconium oxide or cerium oxide, which are allwell-known UV photoprotective agents. Conventional coating agents are,moreover, alumina and/or aluminium stearate. Such coated or uncoatedmetal oxide nanopigments are in particular described in patentapplications EP518772 and EP518773.

The photoprotective agents are generally present in the composition usedaccording to the invention in proportions ranging from 0.1 to 20% byweight, preferably ranging from 0.2 to 15% by weight, relative to thetotal weight of the composition.

The composition used according to the invention may be in any of thegalenical forms normally used in the cosmetics field, and in particularin the form of an optionally gelled aqueous or aqueous-alcoholicsolution, a dispersion, optionally a two-phase dispersion, of the lotiontype, an oil-in-water or water-in-oil or multiple (W/O/W or O/W/O)emulsion, an aqueous gel, a dispersion of oil in an aqueous phase bymeans of spherules, it being possible for these spherules to bepolymeric nanoparticles such as nanospheres and nanocapsules or, betterstill, lipid vesicles of ionic and/or nonionic type; or aqueous or oilygels. These compositions are prepared according to the usual methods.According to this invention, a composition in the form of an emulsion,in particular an oil-in-water emulsion, is preferably used.

The composition used according to the invention may constitute askincare composition, and in particular a cleansing, protecting,treatment or care cream for the face, for the hands, for the feet, forthe major anatomical folds or for the body (for example, day creams,night creams, makeup-removing creams, foundation creams, antisuncreams); a fluid foundation, a makeup-removing milk, a protective orcare body milk or an antisun milk; a skincare lotion, gel or foam, suchas a cleansing lotion.

The invention is illustrated in greater detail by the followingnonlimiting examples.

EXAMPLES 1 TO 4 Demonstration of the Activity on ConstitutiveMelanogenesis

A biological test demonstrated the depigmenting activity of 7 compoundsof formula (I) (compounds 2, 7, 12, 16, 19, 21 and 27).

The modulatory effect of each compound on melanogenesis was measuredaccording to the method described in FR-A-2734825 and also in thearticle by R. Schmidt, P. Krien and M. Régnier, Anal. Bichem., 235(2),113-18, 1996. This test is carried out on a coculture of keratinocytesand melanocytes.

For the compounds tested, the following were determined:

-   -   the cytotoxicity, by estimating leucine incorporation,    -   the inhibitory activity on melanin synthesis, by estimating the        ratio of thiouracil incorporation to leucine incorporation,        relative to 100% of the control (the control corresponds to the        test carried out without test compound). The 1050 values        (concentration for which 50% of the melanin synthesis is        inhibited) were determined.

The test was also carried out with arbutin, niacinamide and kojic acid,which are known depigmenting compounds.

The results are collated in the following table:

Cyto- toxicity on co- Compound culture IC50 Arbutin Non- Not attainedcytotoxic (or greater than 500 μM) Kojic acid 100 μM Not attained (orgreater than 500 μM) Niacinamide Non- Not attained cytotoxic

Non- cytotoxic 4.9 μM

Non- cytotoxic 37 μM

100 μM 25 μM

Non- cytotoxic 32 μM

Non- cytotoxic 29 μM

Non- cytotoxic 410 μM

Non- cytotoxic 128 μM

Compounds 2, 7, 12, 16, 19, 21 and 27 therefore demonstrate theirefficacy in inhibiting melanogenesis and are, moreover, more effectivethan arbutin, kojic acid and niacinamide.

Compound 2 is the most effective compound.

EXAMPLE 5

A depigmenting gel for the skin is prepared, comprising (% by weight):

Compound 2 2% Carbomer (Carbopol 981 from Lubrizol) 1% preservative qswater qs 100%

When applied to the skin, the composition makes it possible to fade outbrown marks.

A similar composition is prepared with compound 3 or compound 11 orcompound 16.

1. A nontherapeutic cosmetic process for depigmenting, lightening and/orwhitening keratin materials, the process comprising applying a cosmeticcomposition to a keratin material, the cosmetic composition comprising,in a physiologically acceptable medium, at least one compound of formula(I):

or its tautomer form of formula (I′):

wherein: R₁ and R₂, which may be identical or different, represent aradical selected from the group consisting of: a) a hydrogen atom; b) asaturated linear C₁-C₂₀ or branched C₃-C₂₀ or unsaturated C₂-C₂₀ alkylgroup, optionally interrupted with one or more heteroatoms selected fromthe group consisting of N, S and O, and/or optionally substituted withone or more groups, optionally identical or different, selected from thegroup consisting of i) —OR₃, ii) —SR₃, iii) —NR₃R₄, iv) —CONHR₃, v)—COOR₃, and vi) a C₅-C₁₂ aryl group optionally substituted with one ormore hydroxyls and/or with one or more C₁-C₈ alkoxy radicals; c) asaturated C₁-C₈ alkyl group substituted with a C₅-C₁₂ aryl radicaloptionally substituted with one or more hydroxyls and/or with one ormore C₁-C₈ alkoxy radicals; and d) a phenyl group optionally substitutedwith one or more hydroxyls and/or with one or more C₁-C₈ alkoxyradicals; R₃ represents a hydrogen atom or a saturated linear C₁-C₅ orbranched C₃-C₅ or unsaturated C₂-C₅ hydrocarbon-based group; and R₄represents a hydrogen atom, a saturated linear C₁-C₅ or branched C₃-C₅hydrocarbon-based group, or an acetyl group; such that R₁ and R₂optionally form, with the nitrogen atom which bears them, a ringselected from the group consisting of pyrrolidine, pyrroline,piperidine, piperazine, morpholine, thiomorpholine and azepine; and alsothe salts thereof, the optical isomers thereof and the racematesthereof.
 2. The process of claim 1, wherein: R₁ represents a radicalselected from the group consisting of: a) a hydrogen atom; and b) asaturated linear C₁-C₁₀ or branched C₃-C₁₀ or unsaturated C₂-C₁₀ alkylgroup, optionally substituted with one or more OR₃ groups; R₂ representsa radical selected from the group consisting of: a) a saturated linearC₁-C₁₀ or branched C₃-C₁₀ or cyclic C₃-C₇ alkyl group, optionallyinterrupted with one or more oxygen atoms, preferably one, and/oroptionally containing one or more groups, which may be identical ordifferent, selected from the group consisting of: i) —OR₃, ii) —NR₃R₄,iii) —CONHR₃, and iv) —COOR₃; b) a phenyl group optionally substitutedwith one or more hydroxyls and/or with one or more C₁-C₃ alkoxyradicals; and c) a saturated C₁-C₅ alkyl group substituted with a phenylradical optionally substituted with one or more hydroxyls and/or withone or more C₁-C₃ alkoxy radicals; R₃ represents a hydrogen atom or asaturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-based group; and R₄represents a hydrogen atom or a saturated linear C₁-C₅ or branched C₃-C₅hydrocarbon-based group.
 3. The process of claim 1, wherein: R₁represents a hydrogen atom or a linear C₁-C₄ alkyl radical optionallysubstituted with one or more hydroxyl groups; R₂ represents a radicalselected from the group consisting of: a) a saturated linear C₁-C₁₀ orbranched C₃-C₁₀ or cyclic C₅-C₇ alkyl group, optionally interrupted withan oxygen atom and/or optionally containing a —CONH₂ group and/oroptionally substituted with one or more hydroxyl groups; b) a phenylgroup; and c) a saturated C₁-C₅ alkyl group substituted with a phenylradical optionally substituted with one or more hydroxyl or C₁-C₃ alkoxyradicals.
 4. The process of claim 1, wherein: R₁ represents a hydrogenatom or a C₁-C₄ hydroxyalkyl group; and R₂ represents a saturated linearC₁-C₁₀ or branched C₃-C₁₀ or cyclic C₅-C₆ alkyl hydrocarbon-based group,optionally interrupted with an oxygen atom and/or optionally containinga —CONH₂ group and/or optionally substituted with a hydroxyl group; aphenyl group; or a saturated C₁-C₅ alkyl group substituted with a phenylradical itself optionally substituted with one or more hydroxyl or C₁-C₃alkoxy radicals.
 5. The process of claim 1, wherein the compound offormula (I) is selected from the group consisting of:N-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-ethyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-isopropyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-propyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2-methylpropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-butyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-pentyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-octyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-nonyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N,N-dimethyl-2-mercaptonicotinamide;N-cyclopentyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-cyclohexyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-cycloheptyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-phenyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-benzyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-[2-(4-methoxyphenyl)ethyl]-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(3-ethoxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2-amino-2-oxoethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N,N-bis(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2,3-dihydroxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(1,3-dihydroxypropan-2-yl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-ethyl-N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-[2-(2-hydroxyethoxy)ethyl]-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(3-hydroxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-[2-(2-hydroxyethoxy)ethyl]-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(3-methoxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N,N-diethyl2-mercaptonicotinamide; EthylN-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]alaninate; EthylN-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]phenyl alaninate; andN-[2-(dimethylamino)ethyl]-N-ethyl-2-thioxo-1,2-dihydropyridine-3-carboxamide.6. The process of claim 1, wherein the compound of formula (I) isselected from the group consisting of:N-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-ethyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-isopropyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-propyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2-methylpropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-butyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-pentyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-cyclopentyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-cyclohexyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-cycloheptyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-benzyl-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-[2-(4-methoxyphenyl)ethyl]-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N,N-bis(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2,3-dihydroxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-ethyl-N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;and N,N-diethyl2-mercaptonicotinamide.
 7. The process of claim 1,wherein the compound of formula (I) is present, alone or as a mixture,in the composition, in an amount of between 0.01 and 10% by weight,relative to the total weight of the composition.
 8. The process of claim1, wherein the composition further comprises at least one adjuvantselected from the group consisting of: water; an organic solvent; acarbon-based and/or silicone oil, of mineral, animal and/or plantorigin; a wax; a pigment; a filler; a dye; a surfactant; an emulsifier;a co-emulsifer; a cosmetic or dermatological active agent; a UV screen;a hydrophilic or lipophilic gelling agent; a thickener; a preservative;a fragrance; a bactericide; a ceramide; an odor absorber; and anantioxidant.
 9. The process of claim 1, wherein the composition furthercomprises at least one active agent selected from the group consistingof: a desquamating agent; a calmative; an organic or inorganicphotoprotective agent agents; a moisturizer; a depigmenting orpropigmenting agent; an anti-glycation agent; a NO-synthase inhibitor;an agent for stimulating the synthesis of dermal or epidermalmacromolecules and/or preventing degradation thereof; an agent forstimulating fibroblast and/or keratinocyte proliferation and/orstimulating keratinocyte differentiation; a muscle relaxant and/ordermo-decontracting agent; a tensioning agent; an anti-pollution agent;a free-radical scavenger; an agent that acts on the microcirculation; anagent that acts on the energy metabolism of cells; and mixtures thereof.10. The process of claim 1, which is suitable for depigmenting,lightening or whitening the skin.
 11. (canceled)
 12. A compound offormula (Ia):

or its tautomeric form of formula (I′a):

wherein: when R₁ represents a hydrogen atom, then R₂ represents aradical selected from the group consisting of unsaturated C₂-C₂₀ alkyls,cyclic C₇ alkyl radicals, saturated linear C₁-C₂₀ or branched C₃-C₂₀alkyls, substituted with one or more identical or different —OR₃ groups,and (C₁-C₂₀)alkylaryls substituted with one or more identical ordifferent —OR₃ groups, and R₃ represents a hydrogen atom or a saturatedlinear C₁-C₅ or branched C₃-C₅ or unsaturated C₂-C₅ hydrocarbon-basedgroup; when R₁ represents a saturated linear C₁-C₁₀ or branched C₃-C₁₀or unsaturated C₂-C₁₀ alkyl group, optionally substituted with one ormore —OR₃ groups, then R₂ represents a saturated branched C₃-C₁₂ orcyclic C₃-C₇ alkyl group, optionally interrupted with one or more oxygenatoms, and R₃ represents a hydrogen atom or an optionally hydroxylated,saturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-based group, andalso the salts thereof, the optical isomers thereof and the racematesthereof.
 13. The compound of claim 12, wherein: when R₁ represents ahydrogen atom, then R₂ represents a radical selected from the groupconsisting of unsaturated C₂-C₂₀ alkyls, saturated linear C₁-C₂₀ orbranched C₃-C₂₀ alkyls, substituted with one or more identical ordifferent —OR₃ groups, and (C₁-C₆)alkylphenyls substituted with one ormore identical or different —OR₃ groups, and R₃ represents a hydrogenatom or a saturated linear C₁-C₅ or branched C₃-C₅ or unsaturated C₂-C₅hydrocarbon-based group; when R₁ represents a saturated linear C₁-C₁₂ orbranched C₃-C₁₀ or unsaturated C₂-C₁₀ alkyl group, optionallysubstituted with one or more —OR₃ groups, then R₂ represents a saturatedbranched C₃-C₁₂ or cyclic C₃-C₇ alkyl group, optionally interrupted withone or more oxygen atoms, and/or optionally containing one or moreidentical or different —OR₃ groups, and R₃ represents a hydrogen atom oran optionally hydroxylated, saturated linear C₁-C₅ or branched C₃-C₅hydrocarbon-based group.
 14. The compound of claim 12, wherein: when R₁represents a hydrogen atom, then R₂ represents a radical selected fromthe group consisting of saturated linear C₁-C₂₀ or branched C₃-C₂₀alkyls, substituted with one or more identical or different —OR₃ groups,and (C₁-C₆)alkylphenyls substituted with one or more identical ordifferent —OR₃ groups, and R₃ represents a hydrogen atom or a saturatedlinear C₁-C₅ or branched C₃-C₅ or unsaturated C₂-C₅ hydrocarbon-basedgroup; when R₁ represents a saturated linear C₁-C₁₀ or branched C₃-C₁₀or unsaturated C₂-C₁₀ alkyl group, optionally substituted with one ormore —OR₃ groups, then R₂ represents a saturated branched C₃-C₁₂ orcyclic C₃-C₇ alkyl group, optionally interrupted with one or more oxygenatoms, and/or optionally containing one or more identical or different—OR₃ groups, and R₃ represents a hydrogen atom or an optionallyhydroxylated, saturated linear C₁-C₅ or branched C₃-C₅ hydrocarbon-basedgroup.
 15. The compound of claim 12, which is selected from the groupconsisting of:N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N,N-bis(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(2,3-dihydroxypropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(1,3-dihydroxypropan-2-yl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-(1,3-dihydroxypropan-2-yl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;N-ethyl-N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide;andN-[2-(2-hydroxyethoxy)ethyl]-2-thioxo-1,2-dihydropyridine-3-carboxamide.